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Inner ear cell therapy targeting hereditary deafness by activation of stem cell homing factors.

Kamiya K - Front Pharmacol (2015)

Bottom Line: Congenital deafness affects about 1 in 1000 children and more than half of them have a genetic background such as Connexin26 (CX26) gene mutation.Stem cell homing is one of the crucial mechanisms to be activated for efficient cell delivery to the cochlear tissue.In our study, monocyte chemotactic protein-1, stromal cell-derived factor-1 and their receptors were found to be a key regulator for stem cell recruitment to the cochlear tissue.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology, Faculty of Medicine, Juntendo University , Tokyo, Japan.

ABSTRACT
Congenital deafness affects about 1 in 1000 children and more than half of them have a genetic background such as Connexin26 (CX26) gene mutation. Inner ear cell therapy for sensorineural hearing loss has been expected to be an effective therapy for hereditary deafness. Previously, we developed a novel strategy for inner ear cell therapy using bone marrow mesenchymal stem cells as a supplement for cochlear fibrocytes functioning for cochlear ion transport. For cell therapy targeting hereditary deafness, a more effective cell delivery system to induce the stem cells into cochlear tissue is required, because gene mutations affect all cochlear cells cochlear cells expressing genes such as GJB2 encoding CX26. Stem cell homing is one of the crucial mechanisms to be activated for efficient cell delivery to the cochlear tissue. In our study, monocyte chemotactic protein-1, stromal cell-derived factor-1 and their receptors were found to be a key regulator for stem cell recruitment to the cochlear tissue. Thus, the activation of stem cell homing may be an efficient strategy for hearing recovery in hereditary deafness.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of the strategy to activate stem cell homing in the mouse cochlea. 1. Upregulation of homing receptors (CCR2, CXCR4) in culture dish by the treatment of MCP-1 or SDF-1. The cells with abundant CCR2 and CXCR4 acquire the higher potentials to be attracted by MCP-1 and SDF-1 (black arrows). 2. The pretreated cells are injected into the perilymph via the semicircular canal. 3. MCP-1/SDF-1 secretion from the target site by pre-treatment with 3-nitropropionic acid (3-NP). 4. Transplanted cells home to the target site.
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Figure 1: Schematic diagram of the strategy to activate stem cell homing in the mouse cochlea. 1. Upregulation of homing receptors (CCR2, CXCR4) in culture dish by the treatment of MCP-1 or SDF-1. The cells with abundant CCR2 and CXCR4 acquire the higher potentials to be attracted by MCP-1 and SDF-1 (black arrows). 2. The pretreated cells are injected into the perilymph via the semicircular canal. 3. MCP-1/SDF-1 secretion from the target site by pre-treatment with 3-nitropropionic acid (3-NP). 4. Transplanted cells home to the target site.

Mentions: To establish an efficient cell therapy for hereditary deafness, we examined treatments that enhanced stem cell homing factors in the cochlear tissue and MSC. We examined inner ear MSC transplantation in CX26 deficient mice, which we developed as a model of hereditary hearing loss (Kamiya et al., 2014). We transplanted the MSCs to the lateral semicircular canal after the induction of stem cell homing factors (SDF-1; MCP-1) in the host cochlear tissue, and their receptors in transplanted MSCs. To enhance the invasion by MSCs of the cochlear tissue, we developed a novel transplant strategy by inducing SDF-1/MCP-1 expression in the host cochlear tissue and enhanced the expression of their receptors, CCR2 and C-X-C chemokine receptor type 4 (CXCR4) in MSCs (Figure 1). With this strategy, we induced efficient invasion of MSCs to the inner ear tissue and differentiation to form gap junctions with CX26 among transplanted MSCs in CX26-deficiente mouse inner ear (unpublished observation).


Inner ear cell therapy targeting hereditary deafness by activation of stem cell homing factors.

Kamiya K - Front Pharmacol (2015)

Schematic diagram of the strategy to activate stem cell homing in the mouse cochlea. 1. Upregulation of homing receptors (CCR2, CXCR4) in culture dish by the treatment of MCP-1 or SDF-1. The cells with abundant CCR2 and CXCR4 acquire the higher potentials to be attracted by MCP-1 and SDF-1 (black arrows). 2. The pretreated cells are injected into the perilymph via the semicircular canal. 3. MCP-1/SDF-1 secretion from the target site by pre-treatment with 3-nitropropionic acid (3-NP). 4. Transplanted cells home to the target site.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307216&req=5

Figure 1: Schematic diagram of the strategy to activate stem cell homing in the mouse cochlea. 1. Upregulation of homing receptors (CCR2, CXCR4) in culture dish by the treatment of MCP-1 or SDF-1. The cells with abundant CCR2 and CXCR4 acquire the higher potentials to be attracted by MCP-1 and SDF-1 (black arrows). 2. The pretreated cells are injected into the perilymph via the semicircular canal. 3. MCP-1/SDF-1 secretion from the target site by pre-treatment with 3-nitropropionic acid (3-NP). 4. Transplanted cells home to the target site.
Mentions: To establish an efficient cell therapy for hereditary deafness, we examined treatments that enhanced stem cell homing factors in the cochlear tissue and MSC. We examined inner ear MSC transplantation in CX26 deficient mice, which we developed as a model of hereditary hearing loss (Kamiya et al., 2014). We transplanted the MSCs to the lateral semicircular canal after the induction of stem cell homing factors (SDF-1; MCP-1) in the host cochlear tissue, and their receptors in transplanted MSCs. To enhance the invasion by MSCs of the cochlear tissue, we developed a novel transplant strategy by inducing SDF-1/MCP-1 expression in the host cochlear tissue and enhanced the expression of their receptors, CCR2 and C-X-C chemokine receptor type 4 (CXCR4) in MSCs (Figure 1). With this strategy, we induced efficient invasion of MSCs to the inner ear tissue and differentiation to form gap junctions with CX26 among transplanted MSCs in CX26-deficiente mouse inner ear (unpublished observation).

Bottom Line: Congenital deafness affects about 1 in 1000 children and more than half of them have a genetic background such as Connexin26 (CX26) gene mutation.Stem cell homing is one of the crucial mechanisms to be activated for efficient cell delivery to the cochlear tissue.In our study, monocyte chemotactic protein-1, stromal cell-derived factor-1 and their receptors were found to be a key regulator for stem cell recruitment to the cochlear tissue.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology, Faculty of Medicine, Juntendo University , Tokyo, Japan.

ABSTRACT
Congenital deafness affects about 1 in 1000 children and more than half of them have a genetic background such as Connexin26 (CX26) gene mutation. Inner ear cell therapy for sensorineural hearing loss has been expected to be an effective therapy for hereditary deafness. Previously, we developed a novel strategy for inner ear cell therapy using bone marrow mesenchymal stem cells as a supplement for cochlear fibrocytes functioning for cochlear ion transport. For cell therapy targeting hereditary deafness, a more effective cell delivery system to induce the stem cells into cochlear tissue is required, because gene mutations affect all cochlear cells cochlear cells expressing genes such as GJB2 encoding CX26. Stem cell homing is one of the crucial mechanisms to be activated for efficient cell delivery to the cochlear tissue. In our study, monocyte chemotactic protein-1, stromal cell-derived factor-1 and their receptors were found to be a key regulator for stem cell recruitment to the cochlear tissue. Thus, the activation of stem cell homing may be an efficient strategy for hearing recovery in hereditary deafness.

No MeSH data available.


Related in: MedlinePlus